The document discusses major depressive disorder (MDD) including its pathophysiology, risk factors, screening methods, diagnosis, assessment of severity and suicide risk, treatment goals and options. It provides details on pharmacologic and non-pharmacologic treatment approaches and outlines stages of treatment. The document also presents several case studies on patients with depression and discusses appropriate treatment recommendations.

1. Pharma D : Atef AL- Saman
Major
Depression
Case Study.

2. ❑ It is also the leading risk factor for suicide, and suicide rates
in the United States have increased by roughly 35% since
1999).
Depression
❑ is a mood disorder characterized by a persistent feeling of
sadness and/or an inability to experience pleasure, with
associated defficulties in daily functioning.
❑ Worldwide, depression is a leading cause of disability and
years of productive life lost . The global economic cost
associated with depression is expected to nearly double by
2030.
Depression significantly affects the prevalence, cost, and
outcomes of many common general medical comorbidities, such
as diabetes

3. ❑major depressive disorder (MDD) is a clinical course characterized by one or more major depressive
episodes without a history of manic or hypomanic episodes.
❑Monoamine hypothesis: Decreased brain levels of the neurotransmitters norepinephrine (NE), serotonin (5-
HT), and dopamine (DA) may cause depression.
❑ Postsynaptic changes in receptor sensitivity: Studies have demonstrated that desensitization or downregulation
of NE or 5-HT1A receptors may relate to onset of antidepressant effects.
❑ Inflammatory hypothesis: Chronic stress and inflammation may alter glutamatergic and GABA transmission.
Neuroactive steroids are a growing area of research for depression.

4. ❑ Which patients are at especially high risk for MDD?
✓ The pathophysiologic cause of depression is unknown, and no clinically useful biological diagnostic markers
or biological screening tests are currently available. However, several known risk factors warrant
consideration:
Should clinicians screen for MDD?
✓ The 2016 U.S. Preventive Services Task Force guidelines recommend screening all adults, including pregnant and
postpartum women as well as older adults, for MDD, provided that adequate resources for diagnosis, treatment, and
appropriate follow-up are available .
✓ Screening is also recommended in adolescents aged 12–18 years. It can be useful in patients who have risk factors for
depression.

5. What screening methods should clinicians use?
➢ The PHQ-2 and PHQ-9 are efficient and widely used tools for depression screening in primary care settings.
✓ The PHQ-9 is a diagnostic and severity rating instrument that can be used after a positive result on the PHQ-2. A PHQ-9
score of 10 or higher has a sensitivity of 74% and a specificity of 91 % in primary care settings.
✓ PHQ-2 Screen for Depression) has a sensitivity of 86% and a specificity of 78% for diagnosing MDD in primary care settings .
Patients screening positive on the PHQ-2 should have a more complete assessment to determine whether they meet the
criteria for MDD according to the Diagnostic and Statistical Manual of Mental
PHQ-2 Screen for Depression
Questions:
• “Over the past 2 weeks, have you felt down, depressed, hopeless?”
• “Over the past 2 weeks, have you felt little interest or pleasure in doing things?”
Scoring: 0 = not at all; 1 = several days; 2 = more than half the days; 3 = nearly every day
Total score = sum of 2 item scores
NOTE: MDD can be distinguished from normal sadness by duration (for example, for 2 weeks, most of the day,
or nearly every day), symptoms (≥5 depressive symptoms), and degree of associated distress or functional
impairment
Diagnosis... The DSM-5 criteria are the standard for diagnosing MDD. The risk for suicide and comorbid
mental and physical illness should be assessed in each patient. If clinicians are uncertain about a patient's
diagnosis, suicide risk, or need for hospitalization, psychiatric consultation is highly recommended.

6. ❑ How can clinicians determine the severity of depression?
A. The PHQ-9 is easily scored to quantify the severity of MDD and is recommended in primary care settings .
B. In addition to suicidality, severe functional impairment, such as inability to provide basic self-care, may suggest the need
for psychiatric consultation or hospitalization

7. ❑How should clinicians assess a depressed patient's risk for self harm including suicide?
✓ Each year, more than 40 000 U.S. citizens die by suicide. Between 1999 and 2018, the age-adjusted suicide rate in the
United States increased by 35%, most notably between 2006 and 2018.
✓ Mental health conditions and addictive disorders such as alcohol use disorders, are the strongest risk factors for suicide in
all age groups they are present in more than 90% of persons who complete suicide .
✓ In patients with major depression previous suicide attempts are the best predictor of completed suicide .
✓ Most patients who die by suicide have seen a physician in recent months .
✓ Clinicians should assess acute risk for suicide at each visit for depression by asking the patient directly about suicidal
thoughts, intent, or plans. In addition, consideration of risk factors and collateral history is important.

8. ❑ Goals of Treatment: Resolution of current symptoms (ie, remission), prevention of further episodes of
depression (ie, relapse or recurrence), and prevention of suicide.
❑ Nonpharmacologic Therapy
➢ Evidence supports efficacy of interpersonal and cognitive behavioral therapy in the treatment of MDD.
➢ Psychotherapy alone is an initial treatment option for mild to moderate depression, and it may be useful when
combined with pharmacotherapy for the treatment of severe depression.
❑ Electroconvulsive therapy (ECT) is a highly efficacious and safe treatment alternative for MDD. The response
rate is about 70% to 90%, and it exceeds 50% for patients who have failed pharmacotherapy.
❑ ECT may be beneficial for MDD that is complicated with psychotic features, severe suicidality, refusal to eat,
pregnancy, or contraindication or nonresponse to pharmacotherapy. Typically, 6 to 12 treatments are
necessary with response occurring in 10 to 14 days. When ECT is discontinued, antidepressants are initiated to
help maintain response.
❑ Vagus nerve stimulation (VNS) was approved by the Food and Drug Administration
❑ (FDA) in 2005 for treatment-resistant depression .
❑ Transcranial magnetic stimulation is a noninvasive and well-tolerated procedure
that is FDA approved for use after one failed trial of an antidepressant.

9. Stages of Treatment in Depression
1. Acute: Initial goals are to achieve symptom control and attain remission.
2. Continuation: Sustained use of antidepressant treatment to prevent relapse of depressive
symptoms. Treatment should continue in this phase for at least 4–9 months.
3. Maintenance: Patients at high risk of recurrent episodes (more than two prior episodes, chronic
symptoms lasting more than 1 year, strong suicidal ideation) should continue pharmacotherapy for
1 year or potentially indefinitely.
❑ In accordance with practice guidelines from the American Psychiatric Association medication should be
prescribed for patients with severe MDD (PHQ-9 score ≥20) given the stronger evidence of efficacy in this
subgroup .
❑ Either medication or psychotherapy may be used in mild or moderate MDD, and a combination of both may be
used in moderate or severe MDD.
❑ The American College of Physicians updated its practice guidelines to recommend CBT or second-generation
antidepressants as initial treatment of mild to severe MDD after a thorough discussion of risks, treatment
benefits and costs, accessibility, and patient preferences.

10. Pharmacologic Treatment

11. CASE1
A 25-year-old female in graduate school who presents to the student health clinic for a routine physical
examination. During her visit, Sara states, “I’ve been feeling pretty down lately and just want to give up.” Her
physical examination is unremarkable and all laboratory tests (complete blood count with differential chemistry
panel and thyroid function tests) are within normal limits. A human chorionic gonadotropin test is negative. Her
medical history is noncontributory, takes no medication, uses a daily multivitamin, and denies drinking alcohol,
smoking cigarettes, or using illicit substances. When asked, She states that she has had increasing periods of
depressed mood during the past few months and often finds herself crying in the morning for no particular
reason. She reports that she has no interest in her old hobbies (playing the piano, mountain biking, gardening).
During the past 6 months her appetite has decreased and she has lost 15 pounds. She feels overwhelmed about
all of her academic work and job and has difficulty sleeping, often waking in the middle of the night and being
unable to fall back asleep. She has no energy during the day and finds it difficult to concentrate or make
decisions.
 According scenario what are the clinical presentation of MMD?
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12. ❑ What are the drug options available for Sara’s depressive symptoms? What considerations should be made when
selecting antidepressant therapy?
➢ Antidepressants can be divided into different categories:
A. Selective serotonin reuptake inhibitors (SSRIs)
B. Serotonin norepinephrine reuptake inhibitors (SNRIs) C. Tricyclic antidepressants (TCAs)
D. Miscellaneous antidepressants (e.g., trazodone, nefazodone, mirtazapine, bupropion)
E. Monoamine oxidase inhibitors (MAOIs) F. Serotonin reuptake inhibitor and receptor modulators
(the newest group)

15. ❑After Sara has been treated for a year she is asking about coming off her escitalopram partly because
she is getting married and considering becoming pregnant.
What would be the most appropriate way to proceed with discontinuation and treatment of depression
during pregnancy?
✓ If antidepressants need to be used, then monotherapy is best; avoid first-trimester exposure, do not stop the
antidepressant abruptly, and do not discontinue prior to delivery due to the high risk of postpartum depression.
✓ she should consider tapering off her escitalopram for several weeks before attempting to conceive. If she becomes
pregnant and her depression returns, the risk to the fetus appears to be quite low with most SSRIs
❑A 56-year-old woman presents with a medical history significant for recurrent major depression and
type 2 diabetes with newly diagnosed neuropathy, obesity, and coronary artery disease. She takes
citalopram 40 mg daily, carvedilol 25 mg twice daily, lisinopril 40 mg daily, and metformin 1000 mg
twice daily. She is tearful during her appointment
and continues to have symptoms of depression despite initial improvement with citalopram. She wants
to change antidepressants.
❑ Which would be most beneficial?
A. Bupropion.
B. Duloxetine.
C. Nortriptyline.
D. Sertraline

16. A 45-year-old woman has a medical history significant for sleep apnea, hypertension, type 2 diabetes, chronic pain,
and bulimia. She is in the clinic today for an assessment of her depressive symptoms and a medication evaluation.
She endorses sad mood, poor appetite (lost 6.8 kg [15 lb]), poor concentration, and feelings of hopelessness and
worthlessness for the past 3 weeks. She has also stopped going to her book club because she is not motivated to get
out of the house, and she has frequent nocturnal awakening. She denies suicidal or homicidal ideation. She denies
any use of alcohol, tobacco, or illicit drugs. She currently takes hydrochlorothiazide, metformin, hydrocodone/
acetaminophen, and aspirin. Her current BMI is 20 kg/m2, and her blood pressure today is 152/94 mm Hg. She
reports adherence to her current medications.
1. Which selective serotonin reuptake inhibitor (SSRI) would most likely interact with her current medications?
A. Citalopram.
B. Fluvoxamine.
C. Paroxetine.
D. Sertraline.
2. 2. Which antidepressant would be most appropriate for her depressive symptoms?
A. Bupropion.
B. Fluoxetine.
C. Mirtazapine.
D. Venlafaxine

17. ❑ It has been 4 weeks since her initial visit with you, and she has been treated with citalopram 20 mg/day in
the morning. She still presents with sad mood, but her insomnia, concentration, and appetite have improved.
However, she still has feelings of hopelessness and worthlessness, lack of motivation, and anhedonia. She has
no adverse effects.
❖ At this point, which is the best recommendation to optimize her therapy?
A. Continue at current dose of 20 mg/day.
B. Increase the current dose to 40 mg/day.
C. Add aripiprazole.
D. Change to a different SSRI.
❑ Six months later, she reports that although her depression symptoms have resolved, she has “trouble” during
intercourse, which is quite disturbing to her. You determine that she has anorgasmia caused by citalopram
treatment.
❖ Which is the most appropriate recommendation at this time?
A. Discontinue citalopram.
B. Add bupropion to citalopram.
C. Change to a different SSRI.
D. Change to vortioxetine.